Samples and data are analyzed from a longitudinal population study conducted from 1965 to 2007 that allows study of the risk factors and effects of diabetes mellitus. Risk factors for obesity, hypertension, and nephropathy are also studied, along with the relationships of these diseases to diabetes and their effects on development of vascular complications and mortality. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. These findings are reported in DK069028 (Genetic epidemiology of diabetes and obesity) and DK069094 (Genetic epidemiology of diabetic complications). Findings related to kidney complications of diabetes are reported in DK069062 (Epidemiology, pathophysiology and treatment of diabetic nephropathy). Other findings published this fiscal year are summarized here. Increasing obesity in children. Most studies describing childhood obesity in the United States are based on cross-sectional surveys and do not include substantial numbers of American Indians (AI). This study describes weight trends and transitions among AI children over a 43-year period (1965 through 2007). In early and late adolescence, weight increased across birth cohorts. Prevalence of obesity among pre-adolescents was 17.5% in the 19551964 cohort and 33.7% in the 19851994 cohort. 74% of children overweight in pre-adolescence in the 19851994 cohort became obese by late adolescence; in the 19551964 cohort, only 43% made this transition. This study describes the rising prevalence of childhood obesity. Children obese in pre-adolescence remained obese in late adolescence, stressing the need for early intervention. Birthweight and incidence of type 2 diabetes by age. We estimated the impact of birthweight on early-onset (age <40 years) type 2 diabetes. Participants who had a recorded birthweight were followed until they developed diabetes or their last examination before the age of 40 years, whichever came first. Among 3039 participants, diabetes incidence increased with age and was greater in the lowest and highest quintiles of birthweight. Adjusted for covariates, the effect of birthweight on diabetes varied over time, with a non-linear effect at 1019 years (p < 0.001) and a negative linear effect at older age intervals (2029 years, p < 0.001; 3039 years, p = 0.003). Higher genetic risk for diabetes, greater BMI and maternal diabetes had additive but not interactive effects on the association between birthweight and diabetes incidence. Preventing diabetes. Knowledge of diabetes risk factors coming from this and other studies led to the hypothesis that type 2 diabetes could be prevented or delayed in adults at high short-term risk. This hypothesis was confirmed in the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial in which many of the participants and investigators in this project participated. We are now in a long-term follow-up phase, the Diabetes Prevention Program Outcomes Study (DPPOS), to assess long-term success with weight loss, reduction in the incidence of diabetes, and effects on diabetes complications. This study is reported in DK075078 (Prevention of type 2 diabetes).